Neuroactive steroids modulate in vitro the Mg(2+)-dependent Ca(2+)-ATPase activity in cultured rat neurons.

1. The in vitro effect of neuroactive steroids on the Mg(2+)-dependent Ca(2+)-ATPase activity in neuronal membranes isolated from primary cell culture of rat cortex was examined. 2. A 1-hr treatment of neuronal cell culture with 17-beta-estradiol (10 pM) and pregnenolone sulfate (1 microM) resulted in an increase in the enzyme activity of as much as 130% and 160%, respectively. 3. Neuroactive steroids moderately decreased the stimulation of the Mg(2+)-dependent Ca(2+)-ATPase activity by 72 nM calmodulin, by 20-30%. 4. The effects of hormones on the ATPase activity were irreversible after extensive washing of the membranes. 5. These results suggest that 17-beta-estradiol and pregnenolone sulfate at physiological concentrations could participate in the regulation of neuronal calcium homeostasis at a membrane level.